Pharmacogenomics Midterm

eSNP

expressed SNP

Exon

A region of DNA that resides with a gene that remains in mature mRNA

Phase 1 enzymes

CYP450 (18 families and 43 subfamilies)

Name 3 technologies that are considered NGS

Rosche/454 (pyrosequencing), Illumina Sequencing (Illumina Dye Sequencing), Ion Torrent (proton sequencing)

RNA

complex compound of high molecular weight that functions in cellular protein synthesis and replaces DNA as a carrier of genetic codes in some viruses

Gene

a DNA fragment encoding an RNA or protein

Single nucleotide variant (SNV)

a DNA sequence variation that occurs when a single nucleotide (adenine, thymine, cytosine, or guanine) in the genome sequence is altered

Pharmacokinetics

a branch of science that determines the movement of drug through the body including the absorption, distribution, metabolism, and excretion (ADME)

Pharmacodynamics

a branch of science that studies the biochemical and physiological impact of medication

Microarray technology

a collection of microscopic DNA spots attached to a solid surface used to detect variations in a gene sequence and to measure the expression levels of large numbers of genes simultaneously

Organic cationic transporter

a family of multi-specific, bidirectional, carrier-type permeases that transport organic cations (OCT1, OCT2, and OCT3)

Pharmacogenomics

a field of research that studies how a person's genome affects how they respond to medications

Microsomes

a fragment of endoplasmic reticulum and attached ribosomes obtained by the centrifugation of homogenized cells.

Drug target

a molecule in the body, usually a protein, that is intrinsically associated with a particular disease process and that could be addressed by a drug to produce a desired therapeutic effect

Base pair

a pair of complementary bases in a double-stranded nucleic acid molecule, consisting of a purine in one strand linked by hydrogen bonds to a pyrimidine in the other. Cytosine always pairs with guanine, and adenine with thymine (in DNA) or uracil (in RNA).

Haplotype

a physical grouping of genomic variants that tend to be inherited together; subset of all alleles on specific chromosomes in the population

Intron

a region of DNA that resides within a gene but does not remain in the mature mRNA

Endoplasmic reticulum

a sac like subcellular structure in eukaryotic cells that are involved in lipid synthesis and serving as the site of drug metabolism

Duplication variant

a sequence change between the translation initiation (start) and termination (stop) codon where, compared to a reference sequence, a copy of one or more amino acids are inserted directly C-terminal of the original copy of that sequence

Promotor

a specific DNA sequence responsible for initiation of a transcription

Diplotype

a subset of all genotypes on homologous chromosome pairs in the population

Duplication alleles

a type of mutation in which one or more copies of a DNA segment (which can be as small as a few bases or as large as a major chromosomal region) is produced

Indel

an insertion or deletion of bases in the genome of an organism

Frequency of alleles

calculated by dividing the number of times the allele of interest is observed in a population by the total number of copies of all the alleles at that particular genetic locus in the population

Sanger method of gene sequencing

chain termination method; sequencing with fluorescent chain-termination ddNTP, size separation by capillary gel electrophoresis, laser excitation and detection by sequencing machine

Nuclear receptor

class of proteins responsible for sensing steroids, thyroid hormones, cholesterol, and vitamins

Variation in drug response

different profiles of drug elimination must be caused by the activity of proteins involved in the drug metabolism. As each protein and its amount in the body are directly determined by one's genes, the variability in drug response must have its roots in one's genome.

Noncoding region

does not encode for proteins; made up of regulatory elements, noncoding RNA genes, introns, pseudogenes, repeating sequences, and telomeres

P-gp

drug transporter that determines the uptake and efflux of a range of drugs

Pharmacogenomic therapy

genome-based drug therapy that combines pharmacology (the science of drug) and genomics (the study of genes and their functions) to achieve effective and safe medication that can be prescribed based on a person's genetic makeup

Phase 2 enzymes

glucoronyl transferase (glucuronidation), sulfotransferase (sulfation), glutathione-S-transferase (glutathione), acetyl transferase (acetylation), acyl transferase (amino acid conjugation), methyl transferase (methylation)

Star alleles

haplotype patterns at the gene level associated with protein activity levels

Drug absorption

how the drug moves from the site of administration to the site of action

Frameshift SNV

insertion and deletion in a DNA sequence that shifts the way the sequence is read

Promoter polymorphism

may modify the transcription factor binding sites, thus affecting gene expression.

Alleles

one of two or more alternative forms of a gene that arise by mutation and are found at the same place on a chromosome

Next generation sequencing

parallel sequencing technology that offers ultra high throughput, scalability, and speed; used to determine the order od nucleotides in entire genomes or targeted regions of DNA or RNA

Negative strand of DNA

reverse complementary to both the positive-sense strand and the RNA transcript

Nonsense substitution

single base change that results in a premature stop codon, or a nonsense codon in the transcribed mRNA, and in a truncated, incomplete, and usually nonfunctional protein product

Missense substitution

single base change that results in an amino acid substitution in a protein

Single nucleotide polymorphism (SNP)

single nucleotide substitution in a DNA sequence with prevalence of greater than 1% of the population

Mutation

single nucleotide variation in a population at the frequency of less than 1%

Transporters

specialized membrane-spanning proteins that assist in the movement of ions, peptides, small molecules, lipids and macromolecules across a biological membrane.

Membrane receptor

specialized protein molecules attached to or integrated into the cell membrane. Through interaction with specific ligands (e.g., hormones and neurotransmitters), the receptors facilitate communication between the cell and the extracellular environment

Genome wide association study

study design for identifying associations between occurring variations in DNA sequence and drug response; often conducted using thousands of participants capturing genetic variation in the form of SNPs across the human genome

Synonymous SNP

substitutions do not result in change of amino acid sequence in the protein

Non-synonymous SNP

substitutions result in change of amino acid in the protein

Major difference between Sanger method and NGS

the Sanger method only sequences a single DNA fragment at a time, NGS is massively parallel, sequencing millions of fragments simultaneously per run

Drug concentration

the amount of drug in a given volume, such as mg/L

Genome

the complete set of DNA (genetic material) in an organism

Pharmacogene

the genes which decide the fate of drugs pharmacology in biological system

Genotype

the genetic constitution of an individual organism

Human genome project

the international research project deciphering the entire DNA sequence of human genome

Drug distribution

the journey of the drug through the bloodstream to various tissues of the body

Copy number variant

the number of copies of a specific segment of DNA varies among different individuals' genomes

Phenotype

the observable traits of an individual organism

Drug metabolism

the process that breaks down the drug

Coding region

the protein-coding genes, which encode for proteins; made up of exons

Regulatory region

the region of a gene where RNA Polymerase and other accessory transcription modulator Proteins bind and interact to control RNA synthesis

Drug elimination

the removal of the drug from the body

Randomized clinical trial

the researchers decide randomly as to which participants in the trial receive the new treatment and which receive a placebo

Organic anionic transporter

the secondary/tertiary active transporter proteins that regulate anion balance in the body. They are primarily expressed in the kidney and liver

Pharmacogenetics

the study of genes that influence the outcome of a drug treatment

Chromosome

threadlike structures made of proteins and a single molecule of DNA

Pharmacogene-based therapy

treatment of disease guided by one's genetic make-up